Purpose. A simplified view of Na+ channels is that they allow action potentials to propagate by causing regenerative and transient increases in Na+ ion permeability. This is characteristic of a widely studied, transient Na+ current which is activated by depolarization and inactivates rapidly. In addition to this rapidly decaying component, we have recently described a slowly decaying Na+-current component in retinal ganglion cells. We report here the activation, steady-state inactivation and tetrodotoxin (TTX) sensitivity of these components. Methods. Voltage-gated Na+ currents were activated and recorded in retinal ganglion cell somata freshly dissociated from adult goldfish using whole-cell patch-clamp techniques. Voltage-gated K+ and Ca2+ currents were suppressed pharmacologically, and capacity and leakage currents were subtracted. Results. Two components of Na+ current appeared to be activated by step-deporalizations from a holding potential of -90 mV to test potentials between -80 mV and +90 mV. One began to activate around -45 mV and was termed transient for 2 reasons: first, its exponential decay was rapid (τdecay ≃ 0.6 ms at -10 mV). Secondly, it was fully inactivated by sustained depolarizations (e.g. to around -30 mV). The second component began to activate near -70 mV, and was termed persistent for 2 reasons: first, its exponential decay was slow (τdecay 2 ∼ 10 ms at -10 mV), and it resisted steady-state inactivation. During depolarizations exceeding 40 ms in duration, this persistent current could be activated. Both transient and persistent currents were completely blocked by application of 300 nM TTX, reversed in polarity near the Na+ equilibrium potential, and were suppressed by substituting external NMG for Na+. Conclusion. Our results show that after blockade of K+ and Ca2+ currents the persistent current following the transient current during long depolarizing voltage pulses is TTX-sensitive Na+ current. Because this current activates at potentials close to resting membrane potential and is resistant to inactivation, it may play an important role in the repetitive firing of action potentials in retinal ganglion cells.
|Original language||English (US)|
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Feb 15 1996|
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